ANNALES
U N I V E R S I T A T I S MARIAE C U R I E - S K Ł O D O W S K A LUBLIN —POLONIA
VOL. XXXVIII, 4 SECTIO AA 1983
Instytut Chemii UMCS Zakład Stereo- i Spektrochemii Kierownik: prof, dr hab. Marian Janczewski
Marian JANCZEWSKI, Władysław MAJEWSKI, Janusz JURCZAK
The Effect of Molecular Structure on the Optical Properties of Sulfoxide Systems.
2-(3’-bromobenzylsulfinyl)-benzoic Acids and Some of Their Derivatives. IV *, '*
Wpływ budowy cząsteczkowej na własności optyczne układów sulfotlen kowych.
Kwasy 2-(3'-bromobenzylosulfinylo)-benzoesowe i ich niektóre pochodne. IV Влияние молекулярного строения на оптические свойства сульфоокисных систем.
Кислоты 2-(3'-бромбензилсульфинил'|-бензойные и некоторые их производные. IV
The problem of the effect of position isomerism of certain substituents and functional groups in aromatic rings on optical properties of aromatic - aliphatic systems containing hetero
atomie chirality centers separated from aromatic fragments of molecules by methylene groups has been studied in our labora
tory on the example of benzylsulfinylacetic acids and their derivatives. The observed optical order in the group of isomeric
The work was partly financed by the Polish Academy of Sciences Nr MR 1-12-1.
Xх Part III: Koziol A., Majewski W., Janczewski M., Acta Crvst,, in press.
68 Marian Janczewski, Władysław Majewski, Janusz Jurczak bromobenzylsulfinylacetic acids ß-4J as well as in the group
of isomeric methylbenzylsulfinylacetic acids [jQ suggested that a single methylene group does not isolate completely the sulfoxide system from the effects caused by introduction of substituents to aromatic ring. The obseived optical and stereochemical relationships encouraged us to further studies in the group of benzylsulfinylbenzoic acids and their homo
logues. A closer determination of optical relationships in this group of still little known systems can be of special interest.
Our investigations were started with a comparative study of chiralooptical properties of 2-(benzylsulfinyl)- benzoic acids and their bromo derivatives with halogen atom in the benzene ring of benzyl group i.e. isomeric 2-(bromobenzyl- gulfinylj-benzoic acids. As a reference system having the character of configurational standard as well as a standard for comparing the measured rotation values we assumed un
substituted 2-(benzylsulfinyl)- benzoic acid arbitrarily assigning the R [б J configuration to dextrorotatory enantio
mer.
In the previous papers the synthesis and some chiraloptical properties of enantiomeric 2-(benzylsulfinylj- benzoic acids and their 4’-bromoderivatives were described.
In the present communication we are reporting the syn
thesis and the determination of principal optical and stereo
chemical properties of enantiomeric 2-(3’-bromobenzylsulfinylJ -benzoic acids.
The Effect of Molecular Structure on the Optical 69
Pig. 1. Structural patterns.
1: R1 = S.CHO.CAH.-Br, 2 о 4
Ci)
R2 = COOH 2: R1 = S0.CH„-C,H.«Br, ć. 0 4
(i)
R2 2 coon
1- R1 = S0-CHo.C,H..Br, 2 0 4
Ci)
R2 2 CO«OCH3
L’ R1 = SO .CHO.C,H..Br, 2 о 4
Ci)
R_2 = CO-NHCH^
1- R1 = SO«CH_.C,H.-Br,
Ci) 264 R2
2 CO.OCH_.CO.C,H..Br 2 о 4 6: R1 = SO*CH„-C<H.*Br, 2 о 4
(-)
R2 2 C0>0CHo’CcH.-NO, 2 о 4 2
1- R1 = S0.CHo«CcH..Br, 2 b 4
C-)
R2 COOH.Bruc.
8: R1 = S0.CH_«CrH.»Br, 2 0 4
C+)
R2 COOH 2: R1 = SO-CH •С<Н.•Br, 2 0 4
C+)
R2 2 COOH•Bruc.
10: R1 = SO • CHO • C,H4 • Br , 2 о 4
C+)
R2 2 COOH 11 : R1 = SO.CH_.CtH.-Br, 2 0 4
C+)
R2 2 CO.OCH^
12: R1 = SO.CH_-C,H -Br, 2 0 4
C+)
R2 =.CO.NHCH^
Ц: R1 = SO.CH„.C,H..Br, 2 0 4
(+)
R2 = CO.OCH_.CO.C,H,-Br 2 о 4 Ц: R1 = SO«CH2«C6H4-Br, ^2 = СО.ОСН,«СЙН,«N0„ ■
2 b 4 2 12; R1 = SO,,.CH„.C,H, .Br, 2 . 2 о 4
Ct).
R2 2 COOH
C+)
16: *3 = CH-C6H4-Br, 17: R = CH.CgH,.Br
70 Marian Janczewski, Władysław Majewski, Janusz Jurczak The starting material in our studies was 2-(3’-'bromobenzyl
mercapto J- benzoic acid (1), which was obtained by coupling 2-mercaptobenzoic acid [ejwith m-bromobenzyl bromide £4,sQ in alcaline medium.
Racemic 2-(3* -bromobenzylsulfinyl)-benzoic acid ( 2 ) was obtained by oxydation of the compound J. with 30% hydrogen peroxide in glacial acetic acid. When mercapto acid 1. was treated with an excess of the oxidizing agent at elevated temperature, a good yield of sulfone 15 was obtained. (The IR spectra confirming the structures of the two oxidation products are shown in the Experimental Part.J. Racemic acid 2 was characterized as its methylamide (4) and methyl (5) » p-bromo
phenacyl (5) and p-nitTobenzyl (б) esters.
Racemic acid 2 was resolved by crystallization of di- astereomeric salts with brucine. Optically active 2-(3’-bromo- benzylsulfinyl)-benzoic acids (8 and 10) separated from the alcaloid salts and purified from diluted ethanol showed a high specific rotation (<£)^°= - 355,0°, 360,0° (ethanol).
The optical purity of enantiomeric 2-(3’-bromobenzylsulfi- nyl)-benzoic acids 8 and 10 was confirmed by comparative stu
dies of the 1HNMR spectra of racemic acid 2 (Fig. 2a) and laevorotatory enantiomer 8 (Fig. 2 b) methvlester mixtures with tris-(3-trifluoroacetyl-d-camphorato)-europium (ill)
(Eu (tfc) ) as a chiral shift reagent.
The presented fragment of 1HNMR spectrum of racemic acid methyl ester mixture (Fig. 2a) with a chiral shift reagent demonstrates diastereomeric differentation (two AB quartets) of methylene group protons. On the other hand on the spectrum (Fig. 2b) of laevorotatory 2-(3’-bromobenzylsulfinyl)-benzoic
The Effect of Molecular Structure on the Optical 71
£---V---Й" «
R,. 2a Plq. 2b
Fig. 2. a - Methylene groups protons "'hNMR spectrum of the mixture of racemic 2- J’-bromobenzylsulfinyl -benzoic acid methyl ester and tris- 3-trifluoroacetyl-d-camphorato - europium III 22:20 mg, b - Methylene groups protons 1HKMR spectrum of the mixture of dextrorotatory 2- J’-benzylsulfinyl -benzoic acid methyl ester and tris- 3-trifluoroacetyl-d-
—camphorato - europium III 21:20 mg
acid methyl ester mixture with Eu(tfc)^ realized under the same conditions this effect is not observable (only one AB quartetJ. That proves enantiomeric 2-f 3’-bromobenzylsulfinyl,) -benzoic acids being optically pure in the range of accuracy (2-3%J of the applied 1HNMR method.
Mixing of antipodes 8 and 10 in equimolar proportion . followed by crystallization caused the regeneration of racemic acid 2« The melting point of the racemate 2 is considerably lower ( t = 24°Cj than that of the antipodes 8 and 10. Ihe IR spectrum of racemic acid 2 was not different in the finger print region from the spectra of enantiomers 8 and 10.
72 Marian Janczewski, Władysław Majewski, Janusz Jurczak The relatively easy resolution of optically inactive compund 2 into enantiomers (s and 10) and the physical properties quoted above indicate that racemic acid 2 belongs to the type of racemic mixture.
Optically active 2-(3’-bromobenzylsulfinyl)-benzoic acids i end 10 possess a. considerable resistance to racemization in alkaline media, but lose quite rapidly the ability to rotate
‘he plane of polarized light in organic solvents in the presence of concentrated hydrochloric acid. Racemization pro- emas ere studied using a mixture (2:1 v/v) of dioxane and
ilute ( 7,5:1, v/v, HC1:H-O) hydrochloric acid as solvent.
rJ.r these conditions the racemization of optically active acids 3 and 10 obeyed the kinetic equation of the first order reactions ( К = r In ). The racemization constants ( к), the activation entropies (ДЗ^) and the activation -enthalpies (ДЯ^) calculated for three temperatures after averaging the kinetic measurements by the last squares method, are shown in Tab. 1.
The activation parameters of the racemization processes have been determined by the classical kinetic methods on the basis of the Erring equation £ic3.
Tab. 1.
Thermodynamic characterization of racemization of the optically active 2-(3’-bromobenzylsulfinyl)-benzoic acids
Racemiza
tion tempe rature 0
j Racemization
;•» constants
! Kx10? sek-1
i u
Activation entropy
Д S^eu
Activation enthalpy ДН^ Kcal/mol, KJ/mol 13 •19,63 + 1,45 -3,40 t 0,29 20,60^0,04 86,23-0,17 15 ,25,22 - 2,00 -3,41 i 0,32 20,60^0,04 86,23-0,17 17 •32,82 t 1,36 -3,43 i 0,16 20,59-0,02 86,19-0,08
The Effect of Molecular Structure on the Optical ... 73 The activation energy (2a) and the preexponential factor (A = Kjj,^) have been determined from the empirical Arrhenius
equation: (К = A x e““a/RT) Ea = 21,170 Kcal/mol, A = 2949 x 9 —1
10 зео . The negative values of the activation entropy (AS
* < O) indicate that in the transition state of the racemiza
tion process additive compounds or intermediates previously proposed for arylalkylsulfoxides by German [j 1,12,1?3 American authors, are formed.
Rac. 2-(3’-bromobenzylsulfinyl)-benzoic acid ( 7. ) according to expectations DO have been transformed by heating with acetic anhydride into optically inactive 3-(3’-bromoohenyl) -4-thia-isochroman-1-one ( 16 ). The structure of 3-(3’-bromo- phenyl)-4-thia-isochroman-1-one ( 16 ) was confirmed by elemental analysis and spectral methods ( the IR spectra are shown in the Experimental Part). In order to know if bromine atom in the benzene ring of the benzylgroup can have some influence on stereochemical course of the rearrangement reaction we have transformed by using acetic anhydride under the same conditions dextrorotatory 2-13’-bromobenzylsulfinyl)-benzoic acid. Cn this way we have obtained dextrorotatory 3-(3*-bromophenvl)-4-thia-
isochroman-1-one ( 17). (c4)p^= + 6,5° (in 96% ethanol), with 58% yield and 8% optical purity. The optical purity of the rearrangement product was determined by studing the 1HNMR spectra of methine group protons in diastereomeric compounds formed with tris-(з-trifluoroacetyl-d-camphorato)-europium
(ill) (Eu (tfc) -j ) using deuterochloroform as solvent.
Taking into accound the previously obtained results by rearrangement of unsubstituted laevorotatoiy 2-(benzylsulfinyl)
C°Jand laevorotatory 2-(4’-bromobenzylsulfinyl)-benzoic acids QJit is possible to observe that the introduction of
4 --- i--- pp
*l W
Fig. 3. Methine groups protons spectrum of the mixture of dextrorotatory 3- 3’-bromophenyl -4-thiaisochroman-1-one and tris- 3-trifluoroacetyl-d-camphorato - europium III
20:50 mg
bromine atom into the molecule of 2- (benzylsulfinyl,)-benzoic acid in the meta position of the benzene ring of benzyl group considerably decreases both the yield and the optical purity of the rearrangement product. It is not excluded that our observations could be interpreted on the ground of the rear
rangement mechanism proposed by Oae and Numata [j 7J. Accumulat
ing a larger number of experimental data will give the possi
bility to drow more general conclusions.
Tab. 2
Rotatory dispersion of dextrorotatory 2-/3’-broracbenzylsulfinyl/ -benzoic acid and some of its derivatives
j. Compound S olvent
olar rotation / ./20
=589,3 ma =579,1 ma = 546,1 ma =5-0,0 ma = 480,0 nm = 440,0 nm = 435,3 nm
' Dextrorotatory j 2-/3’-bromobenzyl- : sulfinyl/-benzoic
A
/ 1347 1349/
1418 /1419/
1676 /1690/
1957
/1969/ ■ 2571 558-2
./5574/ 3725
/3713/
! acid Ch
/ 1181
119'/ 1235
/1257/ 1457
/1493/
1689 /1738/
2252 /2278/
3182
/3199/ 3311
/3333/
D
/ 118
119 / 1245
/1255/ 1479
/1491/
1730
/1735/ 2296
/2282/ 3243
/3220/ 3375 z
/3359/
2 7 117117: ! /1232/1228 /1466/1448 /1706/1693 /2224/2222 /3071/3080
3202 /3192/
T’
/ .1211
1215/ 1279
/1278/ 1503
/1518/ 1754
/1754/ 2293
/2296/ 3175
_____Z2165Z________
3301
Z223S/__________
' Dethy1 ester of i dextrorotatory
■ 2-/3’-bromobenzyl-
A Ch
1314 1240
1374 1303
1639 1551
1911 1809
2512 2356
3511 . 3570
5349 5508 i sulfinyl/ -benzoic
i acid
blt!
1247 1194
1303 1251
1551' 1491
1812, 1738
2395 2289
5010 3200
<0
LGjKX
i.x 1332 1395 1646 1925 2515 3469 3610
i IX thy 1 amide of j dextrorotatory
! 2-/3’-bromobenzyl-
À Ch
1187 824 '
1247 853
1472 1043
1719 1205
2262 1606
3142 2272
GXt-VOKOC'JrxbXeu
О•Ht!
G>,Q
I'S
•H
<t-trdi—1*H•JouJCj AW 888
1029
937 1078
1117 1272
1317 . 1490
175S 1944
2485 2705
2582 2811
CXCOOr1 1177 1360 1575 2057 2677 2931
<D-PW1Фr-ЭГ1Hot?h-PUoojc>04’/ ■>оГнFl,r|ооP<flГно4?,о
.:{IОФ*Fi*Jt*xFI<tIfЧОCXI •Ch
1673
1544 H1J клa V0VI COCO J-»ro COO VJro 4*-J 2349 2113
3073
273? .
....... VI4* ’0VJ hJO VIH CJl'XV(5*U-’F
, sulfinyl/-benzoie 1459 1523 1791 f\> b-» 0 Г0 279Э 3990 4151
! <À C î —
1469 1534 177c 2049 2692 3765 3904
- 145 e 1554 1780 2070 2715 5736 _ —32.47____ _______
!£4фI;-ph»-i<■’Jca:rHQ)O11O4JП11H«M>Я‘rjI>фIlOGJt4fiГ;1J<DO!InГчHr1
1о-P ,o:-,Fc«1î4-эф*.Н
J«н'd1«х<••»d;
•i;-н’
1<н1\iо•доa wо; i
■<an:■}
1613 1433 m .■ — <“•
1
11I
1
1!GJKXK.JОХOC.J• tkotn-1lf\ HHclr-tj
___________! 11111r-iOXC.G)[HL"~t’,0г-ko c(XJГ-ÎrHnj11____________l
2334
-i-- ->h
2135 1 1 1 1 jMIV10VJ -J VI-00 1G3C0--3GX JDOO-F- 1 t 1 KX|4XbX (XJGO1ГХ (O,1 KO(XJoxLTV CXbXLfXCXj! 1 1 1 1 1 1 ! 1
1
1
1
1-----------------U 11î!11f111CXСУ»COf4M-(->kxo]•0r-o-rb’-*■t.'Xvl-j111------------------L
The Effect of Molecular Structure on the Optical 75 In order to obtain a larger comparative material for chiroptical studies we have prepared the following derivatives of dextrorotatory acid 10.: methylamide 12 and methyl ester 11, p-bromophenacyl ester 13 and p-nitrobenzyl ester 14. The mild conditions in which the reaction were carried out were not likely to cause racemization at the asymmetric sulfur atom.
The molar rotations of dextrorotatory acid 10 and its deriva
tives 11. 12, 13 and 14 were determined in spectral region 350«^Л^б23,4 nm using methanol (m), 96% ethanol (e), aceto
ne (A), chloroform ( Ch), and dioxane (D) as solvents. The results of measurements are shown in r.?ab. 2.
As it appears from the comparison of the numerical values given in this table, the nature of the solvent has not con
siderable effect on the value of molar rotation. In the visible part of the spectrum the absolute values of molar rotations in the examined solvents decrease in the following order:
a) free acid: A>E?»D>Ch>M; b) acid methvlamide: A>M>E>
D>Ch; c) methyl ester: A>D>Ch>E; d) p-bromophenacyl ester: A>Ch>E>M>D and e) p-nitrobenzvl ester: A>M>D>E.
Analysis of the numerical data summarized in Table 2 shows that the curves representing function (Л) 2 in the region 435<ГА<Гб23,4 nm for dextrorotatory acid 10 and its derivatives 11. 12, -13 and 14 -are almost straight lines, which leads to the conclusion that the optical rotatory dispersion of the compounds examined (in the visible part of the spectrum) has the character of normal dispersion.
Comparison of the Freudenberg optical shifts presented in Table 3 and molar rotation changes caused by changes in the character of'solvent which are summarized in Table 4 indicates
76 Marian Janczewski, Władysław Majewski, Janusz Jurczak
Tab.5 Molarrotations(k)-'!^1ofp-bromophenacyl(l),p-nitrobenzyl(2)andmethyl(3) estersofdextrorotatory2-(4’-bromobenzylsulfinyl)-benzoicand2-(3’-bromobenzyl sulfinyl)-benzoicacids
0e.
MO
KM OJ 0
m
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co
g •»
H
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cn ir.
V—
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MD 0N>
r~ V“
V- md
0
CM CO to
o> O
Ф MO ir
Й 5— V—
Ö
H O
0 *
T— om OJ
p 0 OJ
o- LTX
4— T—
MO. •>
MO 4^
NM om
LT. K>
V—
LC4•K
OM 03
Ф MD o>
Й MD
0 я— V—
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r~
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1 r-< -H 1 гЧ-Н
* £ O * O CON NM CO N
»-»r-l Й «—К Й 1 >-.0 1 >. Ф C\ U,o CM
The Effect of Molecular Structure on the Optical 77
ester r __ ÿi1-
о* cr> œ Ф > о
VO tn
ł >>1040 о
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Æ W Ф> о 1Гч in tn.
tatory2- acidsand -Р ДЗ Д 4
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»4 к
>. 1 —хТЗ N 1 Д г-ГЧ д eu ф >„ о Ф ДЗ Д CÖ
V y— №
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Й 5 £
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r— V— т—
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don -Р й ц
О ДЗ Ф Bromo-j sulf!-« enzoici t i i i i
й 1 +> 1 гЧ ДЗ CO
* и • >■ 1 •»
Й te ф te, ы-^-ö VO Ю. tn
д чч CD
гЧ 1 <ч 1 о f> о KV г—
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tonш cand ameth
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ее in.
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Effect sulflny benzjfl 1 1 1 Solvent i i i i
_____i 1 Acetone Ф
§ К о
P О I
л -р м
7S Marian Janczewski, .»ładysław Majewski, Janusz Jurczak that spatial configuration of dextrorotatory 2-(з*- bromoben
zylsulfinyl) -benzoic acid is R (+).
Our configuration standard was dextrorotatory 2-(Д’-bromoben
zylsulfinyl)-benzoic acid which spatial structure was determin
ed by the Х-гаУ structural analysis □ 821 as R ( + ).
On the basis of the numerical data ( 340<A<623,4 nm) summarized in Table 2 functions (м) (A) have been calculated for dextrorotatory 2-(3’-bromobenzylsulfinyl)-benzoic acid.
rhese functions have the character of the following four-term equations :
a) in methanol:
(-Г0 = 2<4855163 X Ю9 _ 2.8240959 x 109 + 1.-О9736О7 x 109 л A - (215,o)2 A2 - (245,o)2 A2 - (287,0)2
4.6920609 x 108 A2
b) in ethanol:
z-,\20 = 3.5639914 x 109 _ 3.8559243 x 109 1.2660735 x 109 _ A A2 - (215,Q)2 A2 - (245,o)2 A2 - (287,0)2
7.0227594 x 108
" A2
<■) in acetone:
( - )20 _ 8.5999430 x 109- 9.1079005 x 109 2.4117572 x 109 À A2 - (215,0)? A2 - (245,0)7’ A2 - (287,0)2
1.6024598 x 109 A2 d) in dioxane:
(■ ) 0 - 3.6937208 x 109 _ 5,0928960 x 109 1.9569705 x 109 A A° - (215,0)' A2 - (245,o)° A2 - (287,o)2
2.6008704 x 108 A?
The Effect of Molecular Structure on the Optical ... 79 e) in chloroform:
(„120 _ 2.3932496 x 109 _ 3.^596889 x 109 1.5744317 x 109 _
‘ A A2 - (215,О)2 Л2 - (245,О)2 Л2 - (287,0)2 1.0566437 x 108
A2
The values of molar rotations calculated by means of the above equations are given in brackets in Tab. 2. The agreement between the values calculated and those determined experiment
ally is fairly good.
Functions (m) (A) describing in the rectangular system of coordinates (A is the independent variable) the optical proper
ties of dextrorotatory 2-(3’-bromobenzylsulfinyl)-benzoic acid ( 10) change the sign, and have the extrema ( two maxima and one minimum) with in the range 0<ГА<Л^. Their asymptotes are the Д axis and the straight lines perpendicular to it at points 0, Av A2 and Ay
In order to confirm the validity of the above equations (n)(A)we have determined in acetonitrile the circular dichroism (cd) and the UV spectrum of dextrorotatory enantiomer 10. The CD spectrum shows three strong positive maxima at A = 207 nm ( (G) = '+ 37313,1), A = 215 nm((Q) = + 37652,3) and A= 287 nm
( (Q) = + 47439,4) as well as one strong negative maximum at Д = 245 nm( (Q) = - 18995,8). It is of interest that the CD spectra of optically active 2-(3’-bromobenzylsulfinyl)- and 2-(4
*
-bromobenzylsulfinyl)-benzoic acids are very similar.
■This fact confirms our hypothesis that the enantiomers rotating the plane of palarised light in same direction (in the visible part of the spectrum) have the same configuration.
60 Marian Janczewski, Władysław Majewski, Janusz Jurczak The electronic spectrum shows in the examined region two strong absorption bands located in the region A = 210 and 280 nm((£)?10 = 37309,8, (S) 280 = 3818,2.). A band which should appear in the region A = 245 nm is probably screened by a nonsymr.etric-from the long wave side-shape of the strong band located at A= 210 nm.
It is significant that the wave lenghts of the character
istic points on the circular dichroism curve (Qmax) and the dispersion constants in the four-term equations determining the function (?-J(A)have exactly the same values and that the sings of rotational constants are consistent with those of CD maxima.
It should, however be mentioned that the positive CD maximum at A = 207 nm is not reperesented in the four-term eouations determining the functions (’l)lA).
Analysis of the results of optical measurements leads to the conclusion that dextrorotatory 2-(3’-tiromobenzylsulfinyl) -benzoic acid ( 10 ) shows in the examined spectral range three positive and one negative Cotton effects situated in the region
A= 207, 215, 287 and 245 nm.
The optical effects caused by introduction of bromine atom to the meta position of benzene ring of benzyl group in the region of values, for which optical rotatory dispersion is normal, are not difficult to determine in spite of the pronoun
ced and diverse solvent effect. Dextrorotatory. 2-(3’-bromoben- zylsulfinylj-benzoic acid and its derivatives 11, 12 and 14 in all the solvents used in the measurement show molar rotations lower than those of îhe corresponding unsubstituted with .bromi
ne atom compounds. The relative average proc, decrease of molar rotations % 0^2 for free acid is about - 1,84%; - 6,34% for
The Effect of Molecular Structure on the Optical 81 its N-methylamide; - 3,28>ś for methyl ester and - 10,35>ь for p-nitrobenzyl ester. Introduction of bromine atom into the molecule of 2-(benzylsulfinyl)-benzoic acid in the meta posi
tion of the benzyl group decreases the rotation of the system in spite of its hight molar rotation.
Unambiguous interpretation of the observed phenomena requires further systematic stereochemical studies.
EXPERIMENTAL
The meltings points are uncorrected. The polarimetric measure
ments were carried out by a Perkin-Elmer spectropolarimeter 241-MC using the solutions specified in the text. IR and UV spectra were determined by means of SP-2OO and SP-7CO spectro
photometers. CD spectra were obtained in a JASCO dichrograph.
The compounds were examined in suspensions in Nujal (IR) and in solutions mentioned in the text. 1HNMR spectra were run on a Joel I NM-4H-100 (1OO MHz) instrument in CDC1X as solvent using THS as internal standard( = 0,00 ppm). Elemental analys
es were performed in our laboratory by A. Hoffman.
1. 2-(3’-Bromobenzylmercapto)-benzoic acid (1).
5 g of o-mercapto benzoic acid M dissolved in 250 ccm I
of water alkalized with 5 g KOH was added in small portions with stirring to a solution of 5 g of bromobenzyl bromide Q,9J in 100 ccm of 96Й ethanol. The mixture was stirred for 4 h maintaining the temperature in the reactor at 5O-6O°C, Then the
solution was cooled and acidified to Kongo with diluted (l:1 v/v HC1). A fine crystalline precipitate which soon separated was filtered off, washed with water, dried and crystallized from 96% ethanol (1 g subst./10 ccm solv.).
82 Marian Janczewski, Władysław Majewski, Janusz Jurczak Colourless needles (7,5 g), m.p. 198-199°C. The product is readily soluble in chloroform, dioxane and acetone, sparingly soluble in methanol and 96% ethanol and insoluble in water.
Analysis:
For: C14H11BrO2S (323,2) - Calcd.: 52,0% C, 3,4 % H;
found: 52,2% C, 3,1 % H.
IR (cm"1); 740, 990, 1220 cS C^-H (subst. 1, 2); 700, 800, 880, 1140 <5 CAr-H -(subst. 1, 3); .040 £ Сд -Н ( subst. 1, 2 and 1,3); 1460, 1560, 1580 V C. = C. ; 1430 V CH„; 680 v>0-3; AT c.
1060 "VC^-Br; 900 & OH; 1285, 1310, 1410 £ OH and VC-0;
1670 V C=O(COCH).
2. Racemic 2-(з’-bromobenzylsulfinyl)-benzoic acid 2 . 10 g powdered acid 1. was suspended in 70 ccm of glacial acetic acid. The mixture was cooled to 0°C, was added 1,7 ccm 30% H20, and mechanically shaken at room temperature for 12 h.
Thon two portions of 1 ccm of 30% ^2^2 were introduced to the suspension at 12 h intervals and. it was shaken mechanically at room temperature for 24 h. A crystalline precipitate was filtered
off, washed with water (30 ccm), dried in air and crystallized from 96% ethanol (1 g subst./ 10 ccm solv.). Colourless rods (">,5 g), m.p. 173°C with decomo.
The product is readily soluble in methanol, 96% ethanol and acetone, sparingly soluble in chloroform and dioxane and in
soluble in benzene and water.
Analysis
For: CuH11Br03S (’>39,2)- Calcd.: 49,6% C, 3,3% H;
found: 49,4% C, 3,4% H.
IR (cm"'); 750, 1211 6 CAr-H (subst. 1,2); 690, 800, 880, 1100,
The Effect of Molecular Structure on the Optical ... S3
— ■ ■ ■ I ■ -... — " ■' ■ 1 ■ . ■ ■ 1140 Ó CAr-H (subst. 1,3); 1050 (f C^-H (subst. 1,2 and 1,3);
1470, 1570, 1590 V 0^= C^; 1438 v> CH?i 680 p C-S; 1070 V C^-Br; 1000 V SO; 900 (f OH; 1280, 1300, 1410 Ó CH and V C-0;
1700 V 0=0 (COOH).
4
3. Methyl ester of rac. 2-(3’-bromobenzylsulfinyl)- benzoic acid (з). -•
To a suspension of 4 g powdered acid 2 in 20 ccm of dry ether cooled externally with ice and water was introduced dror- wise with stirring a solution of diazomethane in ether (rrepar - ed from 10 g of N,N’-nitrosomethylurea) until a permanent
coloration appeared. Than the mixture was refluxed 1 h (0aCl„
tube) on a water bath. The solvent was distilled off under reduced pressure (l2 mm Eg, water bath). The solid residue(3 g) was crystallized from methanol (25 ccm). Colorless needles (? r),
m.p. 110°C. The ester is readily soluble in ether and acetone sparingly soluble in methanol and 96% ethanol.
Analysis
For: C15H15BrO3S (353,2) - Calcd.: 51,0% C, 3,7% H;
found: 51,3% 0, 3,5% H.
4. Methyl amide of rac. 2- (3’-brotr.obenzylsulfinvl)- benzoic acid ( £_).
Powdered methyl ester (2 g) of rac. acid 2 was suspended in 30 ccm of 30% methylamine ao. solution and shaken mechanical
ly for 10 h at room temperature. The reaction product was filter
ed off, washed with a water (30 ccm), dried in air and crystal
lized (l g subst./5 ccm solv.) from methanol. Colorless needles (l,5 g), m.p. 191°C. The product is readily soluble in methanol^
sparingly soluble in ether.
84 Marian Janczewski, Władysław Majewski, Janusz Jurczak Analysis
For: C.JL.BrNO-S (352,3) - Calcd.: 4,0% N;
19 14 Z r
found: 3f8% N.
5. p-bromophenacyl ester of гас. 2-(з -bromobenzyl- sulfinyl)-benzoic acid ( ).
*
*
Rac. acid 2 (1,79 g, 5 mmole) and p-bromophenacyl bromide (l,39 g, 5 mmole) were used in esterification which v/as carried out for 3 h in 60 ccm of boiling 98% methanol. The product was filtered off (l,9 g)and crystallized from 96% ethanol (/-0 ccm).
Colorless needles (l,3 g), m.p. 163°C. The ester is readily soluble in chloroform and acetone, sparingly soluble in metha
nol and 96% ethanol.
Anal’/sis
For: C__H.,Br,0.3 (536,3) - Calcd.: 49,3% С, 3,0% H;
found : 49,0% C, 3,2% H.
6. p-'Iitrobenzvl ester of rac. 2-(3’-bromobenzyl
sulf inyl)-benzoic acid ( 6).
Rac. acid £ (l,7 g, 5 mmole) and p-nitrobenzyl bromide (l,1 g, 5 nmol) were used in esterification which v/as carried out for 3 h in 50 com of boiling 98% methanol. The product
(', g) ••.•as filtered off and crystallized from methanol (20 ccm).
Colorless needles (l,1 r), m.p. 145°C. The ester is readily soluble in ethylene chloride, dioxane and acetone and sparingly soluble in methanol and 961 ethanol.
Analysis
For: C21Hl6BrNO_S (474,з) - Calcd.: 2,9% N;
found : 2,8% N.
The Effect of Molecular Structure on the Optical ... S5
7. Brucine salt of laevorotatory 2-(3bromobenzyl- sulfinyl)-benzoic acid (7).
*
A sample of 5,088 g (0,015 mole) of acid 2 was mixed with 5,910 g (0,015 mole) of brucine and the mixture was dis
solved in 90 ccm of 96% ethanol. The hot solution was filtered and was left standing at room temperature for crystallization.
After 24 h the first fraction was filtered off. Needles (5 g), m.p. 118-123°C with decomp., (<£,)^°= - 168,0° (c = 0,1, d = 0,5, <£ = - 0,084°) in 96% ethanol. After two crystallizations of the first fraction from 96% ethanol (l: 10.998 g, 90 ccm, 5g,- 168°, 118-123°C; II: 5.0, 100, 3.0, - 178°, 120-121 ; III: 3.0, 90, 2.0, - 178°, 121 ) the product had physical properties which remained unchanged by further crystallization.
Needles (2 g), m.p. 121°C, = - 178,0° (c = 0.1, d = 0.5, CL = - 0.089°) in 96% ethanol. The salt is readily soluble in acetone and ethyl acetate, sparingly soluble in methanol and 96% ethanol.
Analysis
For: C37H37BrN2O7S (733,7) - Calcd.: 3,8% N;
found : 4,0% N.
8. Laevorotatory 2-(3’-bromobenzylsulfinyl)-benzoic acid (§).
Brucine salt 7 (2 g, m.p. 121°C, (<£)-3° = - 178,0°) was added to 50 ccm of warmed water. The mixture was stirred for several minutes and was carefully acidified to lacmus with 3% HC1. The resulting acid 8 was filtered off and was immediat
ely dissolved in 50 ccm of 3% KOH. The solution was warmed to 500C, filtered and acidified (lacmus) with 3% HOI.
86 Marian Janczewski, Władysław Majewski, Janusz Jurczak The precipitate was filtered off (0,9 g), dried in air and crystallized from 25 ccm of 50% ethanol. Colorless plates (0,6 g), m.p. 192°C (decomp.), (c£)^° = - 355,0° (c = 0,1, d = 0,5, cC = - 0,177°) in 96% ethanol. The product is readily soluble in methanol, 96/ ethanol and acetone, sparingly soluble in dioxane and chloroform and insoluble in water.
Analysis
For: С1ДН11ВгО5Э (339,2) - Calcd.: 49,6% C, 3,3% H;
found : 49,9% C, 3,0% H.
IP. (cm"'); 750, 1210 J C,„-H (subst. 1,2); 690, 800, 880, 1110, 1140 Ô C,r-H (subst. 1,3); 1055 cf C.^-H (subst. 1,2 and 1,3); 1450, 1570, 1590 V Сд^Сдг.; 1*30 \2CH9; 690 V C-S; 1070
\) CAr-Br; 1010 VSO; 900 <j’OH; 1260, 1300, 1420 cf OH and VC-O;
1690 V c=o(coon).
9. Brucine salt of dextrorotatory 2-(3bromobenzyl- sulfinyl)-benzoic acid ( 2).
*
The dorther liquors from the first fraction of brucine salt of laevorotatory 2-(з’-bromobenzylsulfinyl)-benzoic acid (section 7 ) were evaporated on a water bath to 40 ccm. The hot solution was filtered and allowed to stand at room temperature for 24 h.
- resulting precipitate was filtered off. Colorless needles Cq,5 -) n.r. 125-129°C (decomp.), (сЛ)* 0 = + 170,0° (c = 0,1, à = 0,5, ck, = + 0,085°) in 96% ethanol. After three crystal
lizations from 96% ethanol ( I: 4.5 g, 50 ccm. 3.5 g, + 174,0°, 127-128°C; II: 3.5, 50, 3.0, + 178,0°, 128 III: 3.0, 50, 2.5, + 178.0, 128) the physical properties of the salt remain
ed unchanged by further purification. Colorless needles (2,5 g) m.p. 128°C (decomp.), (<£)p° = + 178,0° (c = 0,1, d = 0,5,
= + 0,089° ) in 96% ethanol. The salt is readily soluble in
The Effect of Molecular Structure on the Optical 87 acetone and ethyl acetate, sparingly soluble in methanol, 96%
ethanol and dioxane and insoluble in water.
Analysis
For: C37H57BrN2O7S (733,7 ) - Calcd.: 3,8% N;
found : 3,9% N.
10. Dextrorotatory 2-(3’-bromobenzylsulfinyl)- benzoic acid ( 10).
Brucine salt 2 (2,5 g, m.p. 128OC,(<^)^° = + 178,0°) was converted into free acid as in section 8. Crude acid (1,2 g) was crystallized from 50% ethanol ( 30 ccm). Colorless needles (0,7 g), m.p. 197°C (decomp.), (<ä)2° = + 350,0° (c = 0,1, d = 0,5, oG = + 0,180° in 96/» ethanol. The acid is readily soluble in methanol, 96% ethanol and. acetone, sparingly
■ soluble in chloroform and dioxane and insoluble in water.
Analysis
For: CuH11BrO5S (339,2) - Calcd.: 49,6% C, 3,3% H;
. found : 49,9% C, 3,3% H.
11. Methyl ester of dextrorotatory 2-(3’-bromobenzyl
sulfinyl) -benzoic acid (11).
Acid 10 (2 g) was converted into methyl ester as in section 3. The transformation product ( ’,8 г) was crystallized from methanol (20 ccm). Colorless needles (l g), m.p. 102°C,
= + 338,0" (c = 0,1, d = 0,5, di = + 0,159°) in 96 ethanol. The ester is readily soluble in ether and acetone and sparingly soluble in methanol and 96% ethanol.
Analysis
For: C^H^BrO^S (353,2) - Calcd.: 51,0% C, 3,7%H;
found : 51,1% C, 3,5% H.
